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Chemical exchange sensitive MRI as biomarker of early therapeutic response in glioma patients

Subject Area Medical Physics, Biomedical Technology
Nuclear Medicine, Radiotherapy, Radiobiology
Term from 2020 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 445704496
 
Final Report Year 2024

Final Report Abstract

The project aimed to explore the potential of chemical exchange-sensitive MRI techniques, particularly Chemical Exchange Saturation Transfer (CEST) and Chemical Exchange Sensitive Spin-Lock (CESL), for assessing early therapeutic responses in glioma patients. The main objectives of the project included integrating protein-weighted CEST-MRI into clinical protocols at 3T MRI, evaluating its potential for early therapy response in a clinical cohort of glioma patients, and investigating glucose-enhanced CESL-MRI at 7T and 3T MRI for early therapeutic response. Despite challenges posed by the COVID-19 pandemic, which delayed patient recruitment, significant technical developments have been achieved and important results were obtained in the clinical investigations. Eight peer-reviewed publications, which acknowledged DFG support, contributed to the scientific understanding of CE-sensitive MRI. Technical developments included the introduction of an evaluation pipeline and automated quality assurance checks, ensuring reliable data analysis. Additionally, advanced statistical tools and 3D segmentation techniques were developed, facilitating a detailed analysis of CEST-MRI data. The project also explored regional differences in CEST contrasts and developed a physically interpretable model (PIM) to enhance understanding of APTw contrast mechanisms. The findings indicated that amides and rNOE were dominant contributors to the APTw contrast, providing insights into the biophysical underpinnings of CEST imaging. The project successfully integrated CEST-MRI into clinical protocols, with 156 glioma patients participating in the study. Early results of an interim analysis indicated that that the less specific ssMT- (MTconst ) and APT-weighted (APTwasym) contrasts allowed a more accurate assessment of treatment response and a more precise prediction of survival in the early observation interval after completion of radiotherapy compared to the more specific APT- and ssMT-weighted contrasts (APTMTRRex) and (MTMTRRex). Furthermore, the signal influence of therapeutically induced changes, such as radionecrosis, tissue edema, and small hemorrhages, have been further investigated to determine their contributions to CEST contrasts. In glucose-enhanced MRI examinations at 7T, motion artifacts were previously addressed by developing a robust 3D acquisition protocol. However, at 3T, the glucose signal was too weak to justify patient examinations, as the change in relaxation rate (ΔR1p) was minimal, making the method currently unreliable for clinical use at 3T. The project has advanced our community’s understanding of both the value of different ES metrics for early therapy response assessment as well as the identification of potential confounders. The performed studies demonstrated the value of the protein-weighted CEST technique in assessing therapy response, thereby motivating and justifying its further clinical application of this contrast agent- free imaging method. Ongoing collaborations and additional analyses will continue to expand knowledge in this area, with the goal of improving the clinical assessment of brain cancers through CE-sensitive MRI techniques.

Publications

 
 

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